Dietary fatty acid-induced alterations of hepatic microsomal drug metabolism

Abstract

Male and female weanling, Sprague-Dawley rats were fed synthetic fat-free (FF) or corn oil-containing diets for 3 weeks. The apparent K m and V max for the metabolism of ethylmorphine and hexobarbital were lower in washed hepatic microsomes from male rats fed a FF diet than in rats fed diets containing 3 or 10 per cent corn oil. The apparent V max for aniline hydroxylase was also depressed by feeding a FF diet to male rats, although aniline K m was not altered. Feeding a FF diet to female rats decreased V max for both hexobarbital oxidase and aniline hydroxylase, but the apparent K m for the substrates was not changed. Gas-liquid Chromatographie analysis of fatty acids derived from microsomal membranes revealed marked alterations in the relative content of fatty acids in response to FF feeding. Content of cytochrome P-450 was lower in both male and female rats fed a FF diet. Associated with the decreased cytochrome P-450 content were decreases in the ability of microsomes to bind aniline and hexobarbital. A qualitative change produced in cytochrome P-450 was indicated by a decrease in the ratio of ethyl isocyanide peak heights (455:430 nm) in microsomes from FF-fed rats.